DESCRIPTION (Applicant's Abstract): Increased vascular permeability is an important factor contributing to the development of ischemic brain damage and edema. The goal of this research is to examine the effect of hypoxia on permeability characteristics of the blood-brain barrier. The first Aim is to elucidate the functional changes in BBB permeability after various intervals of hypoxia and simulated reperfusion in vitro. The second is to determine the localization and expression of the calcium-dependent cytoskeletal protein, F-actin, and the calcium-dependent cellular adhesion molecule, E-cadherin, after hypoxic insults. The third Aim is to investigate endothelial cell apoptosis by performing nuclear degradation measurements and examining BCL-2 expression. The focus of this proposal is on non-neuronal mechanisms that contribute to stroke pathology. The studies will provide new information about mechanisms that may contribute to permeability changes observed after ischemia.